Acne vulgaris: The metabolic syndrome of the pilosebaceous follicle Bodo C. Melnik, MD  Clinics in Dermatology  Volume 36, Issue 1, Pages 29-40 (January 2018) DOI: 10.1016/j.clindermatol.2017.09.006 Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. 1 The mTORC1 family. Acne vulgaris and related mTORC1–driven diseases of civilization. BMI, body mass index; mTORC1, mechanistic target of rapamycin complex 1. Clinics in Dermatology 2018 36, 29-40DOI: (10.1016/j.clindermatol.2017.09.006) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. 2 mTORC1-driven metabolomics in acne vulgaris. Puberty and Western diet increase insulin/insulin-like growth factor 1 (IGF-1) signaling, which enhances androgen (A) synthesis and androgen receptor (AR) activation as well as activation of the kinase AKT. AKT-mediated phosphorylation and thus inhibition of tuberous sclerosis complex 2 (TSC2) activates mTORC1. Androgens via mTORC2-mediated activation of AKT as well as AR-reduced DEPTOR expression further enhance mTORC1 activation. AKT suppresses FoxO transcription factors that suppress AR, SREBP1 and mTORC1. mTORC1 activates the key lipogenic transcription factor sterol response element binding factor 1 (SREBP1), that induces the expression of acetyl CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid de novo synthesis. SREBP1 also induces the expression of Δ6-desaturase and stearoyl CoA desaturase that generate sapienic acid (C16:1Δ6) and oleic acid (C18:1), respectively. Oleic acid promotes Propionibacterium acnes biofilm formation increasing P acnes lipase activity and free fatty acid release and disturbs follicular keratinization. Free palmitic acid (C16:0) and P acnes-derived lipoteichoic acid via Toll-like receptor 2 (TLR2) stimulation activate the NLRP3 inflammasome promoting T helper cell 17 (Th17 cell-driven inflammation. Replacement of linoleate in acylceramides of infundibular keratinocytes by sapienic acid and palmitic acid disturbs follicular barrier function further enhancing follicular inflammation. IL, interleukin. Clinics in Dermatology 2018 36, 29-40DOI: (10.1016/j.clindermatol.2017.09.006) Copyright © 2017 Elsevier Inc. Terms and Conditions